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Parasite Infection, Carcinogenesis and Human Malignancy – PMC

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity. 1. Introduction Cancers are characterized by uncontrolled growth of abnormal and transformed cells, which can invade adjacent tissues. The global burden of cancer in 2012 was estimated to be 14.1 million new cases and 8.2 million related deaths (WHO, 2015). Six types of cancers including lung, liver, stomach, colorectal, breast, and esophagus cancers are the most common causes of cancer death; four of these (liver, stomach, colorectal, and esophagus cancers) are often associated with distinct infectious diseases (WHO, 2015). Multiple factors can significantly contribute to carcinogenesis (WHO, 2015). Meetings of experts from diverse fields of cancer research held at the International Agency for Research on Cancer (IARC) from 2008 to 2009 have reassessed and classified human carcinogens into “discrete” groups including infectious pathogens (Bouvard et al., 2009, IARC, 2012). Infections with eleven species of pathogens associated with cancers are classified as Group 1 carcinogens, definitely “carcinogenic to humans”, by the IARC. These agents include Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium, human papillomavirus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1), human herpes virus type 8 (HHV-8) and human immunodeficiency virus type 1 (HIV-1) (Bouvard et al., 2009, IARC, 2012, de Martel et al., 2012). Among parasitic diseases, infections with the two fish-borne liver flukes of the family Opisthorchiidae (trematodes), specifically Opisthorchis viverrini and Clonorchis sinensis, can induce cholangiocarcinoma, and infection with the blood fluke Schistosoma haematobium may cause cancer of the urinary bladder (Bouvard et al., 2009). Although malaria per se is not considered carcinogenic to humans by the IARC, the geographical association between the occurrence of malaria and that of Burkitt lymphoma provides a clue that malaria plays as a co-carcinogenic factor, together with EBV infection, for the development of Burkitt lymphoma (Molyneux et al., 2012). Other species of the genera Opisthorchis and Schistosoma are thought likely to be carcinogenic (Sripa et al., 2007, Pakharukova and Mordvinov, 2016). Intriguingly, Trypanosoma cruzi, the etiological agents of Chagas disease, displays apparently paradoxical roles in malignancy in exerting carcinogenic and anticancer properties (Krementsov, 2009, Sacerdote de et al., 1980). Potential causative roles of other parasitic infections have been postulated (Machicado and Marcos, 2016). Here, we summarize current concepts and facts on associations of parasite infections, namely schistosomiasis, opisthorchiasis, clonorchiasis, strongyloidiasis, malaria, and Chagas disease with human cancers and review mechanisms by which parasites may promote, or impede carcinogenesis (Table 1). Table 1 Parasitic pathogens and infection-associated malignancy. Parasitic pathogens Disease Endemic areas Associated cancer Proposed mechanism of carcinogenesis Blood flukes Schistosoma haematobium Schistosomiasis sub-Saharan Africa Urinary bladder cancer, adenocarcinoma, squamous cell carcinoma Inflammation, oxidative stress caused by parasite-derived molecules Schistosoma japonicum Schistosomiasis sub-Saharan Africa Colorectal cancer, rectal cancer, squamous cell carcinoma, membranous nephropathy, metastatic lung cancer Inflammation, oxidative stress caused by parasite-derived molecules Schistosoma mansoni Schistosomiasis sub-Saharan Africa Adenocarcinoma, colorectal cancer, hepatocellular carcinoma Inflammation, oxidative stress caused by parasite-derived molecules Liver flukes Opisthorchis viverrini Opisthorchiasis Southeast Asia Cholangiocarcinoma Inflammation, oxidative stress caused by parasite-derived molecules, cell proliferation, H. pylori mediated induction Clonorchis sinensis Clonorchiasis China, Korea, northern Vietnam Cholangiocarcinoma Inflammation, oxidative stress caused by parasite-derived molecules, cell proliferation Opisthorchis felineus Opisthorchiasis Europe and Russia Cholangiocarcinoma Inflammation, oxidative stress caused by parasite-derived molecules, cell proliferation Plasmodia species Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi Malaria sub-Saharan Africa, Southeast Asia Burkitt lymphoma (indirect carcinogenicity) Expansion of the EBV-infected B cell population, Suppression of EBV-specific T-cell immunity, Reactivation of EBV, AID-dependent genomic translocation Strongyloides stercoralis Strongyloidiasis sub-Saharan Africa, South and Central America Southeast Asia HTLV-1 induced lymphomas/leukemias (indirect carcinogenicity) Colon adenocarcinoma Stimulate HTLV-1 replication, Oligoclonal expansion of HTLV-1-infected lymphocytes Trypanosoma cruzi Chagas’ disease South and Central America Gastrointestinal cancer, Uterine leiomyoma Unknown Open in a separate window Go to: 2. Schistosomiasis and Cancer Schistosomiasis is a neglected disease caused by infection with blood fluke trematodes of the genus Schistosoma. Out of 207 million cases of schistosomiasis currently estimated worldwide, 90% occur in sub-Saharan Africa (Steinmann et al., 2006). Schistosomiasis is considered the most important helminth parasite of humans in terms of morbidity and mortality. The five species of Schistosoma that infect humans are Schistosoma haematobium, S. mansoni, S. japonicum, S. intercalatum, and S. mekongi. Most human infections are due to S. haematobium, S. mansoni, and S. japonicum. Of those, S. haematobium is the most ubiquitous species in Egypt and in sub-Saharan Africa and causes urogenital schistosomiasis (UGS). The prevalence of schistosomiasis is associated with exposure-related factors, in particular with a favourable environment for the imperative intermediate host snails, sub-optimal sanitation infrastructure, and host genetic factors. Adult worms are usually found in human hosts; their interactions with the host and parasite-derived products including their eggs strongly induce carcinogenesis (Brindley et al., 2015). With regard to schistosomiasis at large, clearly UGS i.e. chronic infection with S. haematobium, is carcinogenic and thus classified as a Group 1 carcinogen by the IARC (IARC, 2012). Any carcinogenicity of infection with other schistosomes is far less evident. Liver and colorectal cancers and lymphoid tumors may be associated with chronic schistosomiasis. Nonetheless, infection with S. japonicum is classified by the IARC as Group 2B, i.e. possibly carcinogenic to …
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Veterans

5 Ways Christians Can Help Veterans and Their Families

It’s clear: God has called upon you to help and love others and to spend your time on earth making life better for your brothers and sisters. This is undoubtedly true for your desire to help service members, veterans, and their families — they provide a service to the U.S., and if your heart is telling you to assist them, Christ must have put it in your path for a reason. Let’s take a look at how a Christ-honoring member of the community can help veterans, service members, and their families the most: 1. Provide transportation to vets in your area The U.S. Department of Veterans Affairs (VA) organizes a volunteer transportation network (VTN), which allows volunteers from the community to provide rides (either in government-owned vehicles or your own) to veterans who need to get to medical and mental health treatment appointments. You simply need to apply using the form on the VTN website. 2. Help a veteran purchase a home According to an Urban Institute report, nearly 78 percent of veterans own homes, but there is always someone who could use your help with buying a home and navigating the steps of acquiring a loan. The VA offers several kinds of loans for veterans, with the main benefits being that veterans aren’t required to have a down payment ready at the time of purchase, interest rates remain competitive with market prices, and you don’t have to worry about acquiring private mortgage insurance. Help a veteran by checking to see if they qualify for a VA loan and helping them apply for it if so. 3. Get a veteran enrolled in education As of 2016, 18.6 percent of veterans had a bachelor’s degree, and only 8.9 percent had obtained a master’s degree. One way you can help a veteran is to assist them in connecting with a master’s program like criminal justice or psychology — or even business! — so they can advance their career after their time in the service has ended. Attending online classes makes it easy to work full-time and earn a degree at the same time! 4. Spend time with a veteran Sometimes, all folks need is a companion and someone they can talk to. Spending time with someone who has served in the military can not only be good for them; it can be a great thing for you as well. Some veterans are socially isolated when they leave the service, and having a human companion to talk to and share stories with can be a valuable thing indeed for these folks. 5. Take your dog to visit a vet While you’re spending time with a veteran or stopping by the VA to do some volunteer work, why not take your pet? Getting your dog registered with the American Kennel Club as a therapy animal could be a great way for you to assist vets and help bring affection and joy to their lives. Animal therapy has been shown to reduce anxiety, depression, pain, and fatigue — plus it’s wonderful to see the smile on others’ faces when they see your pet. Go forth and do good Following your chosen path and helping folks in need, especially service members and their families, is a good way to honor Christ and practice his teachings to bring more love and worship to the world around you. If your church needs financing, Griffin Capital Funding can help you find exceptional loans at unrivaled rates. Call (800) 710-6762.